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随着炔雌二醇临床适用范围的扩大和畜牧渔业中的滥用所导致的环境污染,使得建立准确、简便、快速的体内检测方法和开展对雌二醇的胚胎发育毒理研究愈显重要。本文以17α-乙炔雌二醇(17α-ethynylestradiol,EE2)为代表化合物,利用模式动物斑马鱼研究了EE2的致畸性、靶组织和靶基因及其对胚胎心律的影响。结果表明,EE2的半数致畸浓度(TC50)为0.8μg.mL-1,半数致死浓度(LD50)为3.3μg.mL-1;其致畸靶位涉及脑和眼、心、肌肉、骨骼、色素和内脏。EE2可导致胚胎心率异常。胚胎对EE2敏感期主要在器官形成期之前,且具有时间积累效应。RT-PCR结果显示,EE2可抑制头部发育基因如boz,促进躯干和尾部发育的基因如ntl、spt和成形素shh基因,干扰多功能的Nodal信号基因cyc、sqt和oep。本研究利用斑马鱼建立了快速、有效体内检测炔雌二醇类化合物胚胎毒性的方法。
With the clinical application of ethinylestradiol and the environmental pollution caused by the abuse of livestock and fisheries, it is important to establish accurate, simple and rapid in vivo detection methods and carry out the embryonic development of estradiol toxicity research. In this paper, 17α-ethynylestradiol (EE2) was used as a representative compound to study the teratogenicity, target tissue and target genes of EE2 and its effect on embryonic heart rhythm. The results showed that the half-teratogenic concentration (TC50) of EE2 was 0.8μg.mL-1 and the LD50 was 3.3μg.mL-1. The teratogenicity of EE2 involved the brain and eye, heart, muscle, Pigments and offal. EE2 can lead to embryonic heart rate abnormalities. EE2 sensitive period of the embryo mainly in the organ formation period, and the accumulation of time effect. RT-PCR results showed that EE2 inhibited the development of head development genes such as boz, genes that promote trunk and tail development such as ntl, spt and the shsh gene, interfering with the multifunctional Nodal signaling genes cyc, sqt and oep. In this study, we established a rapid and effective method for the detection of embryotoxicity of ethinyl estradiol in zebrafish.